A Study to Evaluate Safety and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate Safety and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation (NCT01978912), a non-randomized phase 1, phase 2 study. The primary outcome is Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs.

2. Clinical Question

3. Trial Design

This completed study was registered as a Phase 1 and Phase 2 investigation of KTP-001 in subjects with lumbar disc herniation. Its official title describes an open-label, non-controlled, single ascending dose study. The allocation was non-randomized, the masking was none, and the study model was sequential. These design features describe a series of dose cohorts rather than a randomized comparison against a control treatment.

The four cohorts received one-time intradiscal injections of KTP-001 at 5 μg/disc, 15 μg/disc, 50 μg/disc, or 150 μg/disc. The registry lists enrollment of 24. The design sought to evaluate safety and tolerability, pharmacokinetics, and exploratory efficacy. The primary safety outcome was assessed over 24 months and covered adverse events along with imaging, examination findings, and vital signs.

In a sequential design, cohorts are enrolled or assessed in sequence, but the detailed operational rules for progression between doses are not reported in the registry record. The record also does not report the rationale for the dose levels, the dose-escalation decision criteria, or whether decisions were made using formal statistical rules. Those details should not be inferred from the cohort labels alone.

Because the trial was open-label and non-controlled, there was no blinded concurrent control to provide a reference for changes over time or for events that might occur independently of treatment. The record identifies Teijin America, Inc. as sponsor and lists the study status as completed. It does not report enough information to assess how participants were selected for each cohort or how the study handled departures from the planned sequence.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs, measured over 24 months.

The primary outcome is a participant count for safety assessed by adverse events, MRI, X-ray imaging, physical examination, neurologic examination, and vital signs over 24 months. The registry states that clinically significant changes were recorded as adverse events and described in the adverse-events results. It defines a treatment-emergent adverse event as one that was absent before study drug treatment but appeared after treatment, or one already present at treatment initiation that worsened in severity during treatment. Events related to MRI, X-ray imaging, physical examination, and neurologic examination are identified as adverse events of special interest.

Safety outcomes are used in early-phase studies to describe the kinds and counts of events observed during treatment and follow-up. A participant count is a descriptive measure: it indicates how many participants had an event under the outcome’s definition, but it does not by itself establish why the event occurred. In an uncontrolled study, such counts cannot be compared with a concurrent control group to distinguish treatment-associated events from background events or changes that might have occurred over time.

The registry record identifies the endpoint and its timeframe, but does not report a complete set of primary endpoint results in the registry record for this analysis. The adverse-event counts reported by cohort are informative descriptive safety data, not a test of treatment efficacy.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a count of participants, and the event-count results are presented by dose cohort. For this kind of binary outcome, each participant is classified according to whether the event definition was met. The resulting count is easy to interpret descriptively, but it does not convey all details about timing, recurrence, severity, or causal attribution unless those are reported separately.

What does a participant count tell the reader?

A count states how many participants met the recorded event definition in a cohort. It is distinct from an event count when one participant can experience the event more than once: the endpoint is described as participants with an event. When a count is shown with the cohort denominator, the reader can see the observed number relative to those at risk in that cohort. The count remains a description of the observed study participants, rather than a guaranteed estimate for a wider population.

Counts are especially useful for a safety-focused study because they make uncommon or serious reported events visible without relying on a single average outcome. However, small cohorts make estimates imprecise. A small change in the observed count can substantially change the apparent pattern, and a count of zero does not prove that the underlying event cannot occur. General statistical principle: uncertainty intervals can communicate the range of values compatible with observed data, but no such interval is reported in the registry entries available for this analysis.

Why does the design matter for interpretation?

Random allocation, when used, helps balance participant characteristics between groups on average. This study was non-randomized and had no control group, so dose cohorts should not be treated as equivalent groups differing only in dose. Sequential enrollment may also mean that cohorts were observed at different points in study conduct. The registry record does not report the procedures governing progression between cohorts or whether cohort differences were adjusted for analytically.

Open-label conduct means treatment assignment was not masked. General statistical principle: knowledge of treatment can influence reporting, assessment, or decisions about whether a finding is clinically significant, particularly for outcomes involving judgment. This does not establish that such bias occurred in this study; it identifies a possible limitation of the design. The registry defines treatment-emergent events and adverse events of special interest, but does not report the adjudication procedures or the criteria used to assess relatedness.

What analyses are reported?

The registry entries list zero analyses. They do not report inferential tests, confidence intervals, adjusted estimates, or an analysis plan for the safety counts. Without those results, the cohort counts should be treated as descriptive rather than as statistically tested differences. The record also does not report how repeated events, incomplete follow-up, or missing outcome assessments were handled.

General statistical principle: a confidence interval expresses uncertainty around an estimate under specified assumptions. A p-value, when used, assesses compatibility of data with a statistical model’s null hypothesis; it does not measure the probability that a treatment works or that a finding is due to chance. Neither type of statistic can resolve the lack of a randomized comparator or correct for unreported outcome data. Since the registry entries contain no such estimates, none should be inferred from the counts.

What does sequential dosing contribute?

A sequential ascending-dose structure can organize safety observation across dose levels. It does not automatically create a formal dose-response analysis. To evaluate dose-response, an analysis would need to define the trend or contrast of interest and account for the design and uncertainty. The registry record does not report such an analysis. Differences in cohort counts, on their own, cannot determine whether the dose caused a change in event frequency.

The record’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event calculations are expressed as participants per arm. These are planning assumptions, not observed trial results or observed power. They should not be read as the study’s original design justification: that justification is not reported in the registry record. No planning value should be interpreted as evidence about the reliability of the observed safety counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists secondary outcomes for participants with serum concentrations of KTP-001 below the limit of quantification and participants with anti-KTP-001 antibody. It also reports a total of 10 outcome measures, but the statistical analysis information does not describe how those outcomes were analyzed or how results across outcomes were interpreted.

Multiplicity arises when several outcomes, time points, or comparisons are examined. General statistical principle: as the number of statistical tests grows, the chance of at least one apparently unusual result can increase if each test is interpreted independently. Researchers may address this with prespecified primary outcomes, adjusted testing procedures, or an explicitly exploratory interpretation. The registry record does not report a multiplicity strategy, so it is not possible to determine whether any adjustment was planned or used. The exploratory efficacy aim should therefore not be treated as confirmatory evidence.

The registry entries do not report missing-data methods, analysis populations, or the handling of participants who might have missed assessments or discontinued follow-up. They also do not specify whether results were analyzed according to the cohort initially entered or according to treatment received. These details matter because outcome counts can depend on who was included and how unavailable assessments were treated.

General statistical principle: missing observations can reduce precision and can also bias estimates if their absence is related to participant status or outcome. The direction and size of any such effect depend on information not reported. The enrollment and cohort counts do not establish that every planned assessment was available for every participant over the 24-month timeframe. No assumption about complete follow-up or the cause of missingness is warranted from this record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: appendicitis (16.7%), diverticulitis (16.7%), urinary tract infection (16.7%), menorrhagia (16.7%).

The serious adverse-event figures are participant counts by cohort: 1 of 6 in Cohort 1, 2 of 6 in Cohort 2, 1 of 6 in Cohort 3, and 0 of 6 in Cohort 4. The registry records zero deaths in each cohort. It also lists appendicitis, diverticulitis, urinary tract infection, and menorrhagia as serious adverse-event terms, each reported at 16.7%. The record does not specify which cohort each term belongs to, so the terms should not be assigned to a particular dose group.

These are descriptive observations, not comparative estimates. Because there was no randomized control group, the counts cannot establish whether KTP-001 caused an event or whether the pattern differs from what would have occurred without treatment. The registry entries do not report event-relatedness judgments for these serious events. A serious event is not necessarily a treatment-related event.

Small cohort counts are also imprecise: observing no deaths in a cohort does not establish that the risk is zero. Conversely, an event observed during the study is not by itself proof of a treatment effect. The proper reading is limited to what was recorded among participants in these cohorts.

12. What the Result Does, and Does Not, Mean

The results describe safety observations in a completed, open-label, non-controlled study of KTP-001 in subjects with lumbar disc herniation. The registry reports serious adverse-event counts across the four sequential dose cohorts and zero deaths in each cohort. It also reports other adverse-event counts and lists several serious adverse-event terms. These findings characterize events recorded during the study; they do not establish why the events occurred.

The study’s design is important to the meaning of those observations. Without a concurrent control group, the event counts cannot be compared with a group that did not receive KTP-001 or received another treatment. Non-random allocation also means that cohort differences cannot be assumed to reflect dose alone. The counts cannot show that a higher dose is safer or less safe, and they do not establish a dose-response relationship.

The registry’s primary outcome concerns safety assessment through adverse events, imaging, examinations, and vital signs over 24 months. The event counts reported in the available record do not provide a complete account of all those assessments. Nor does the information provide an efficacy estimate, an inferential test, or an uncertainty interval. The study’s exploratory efficacy aim should not be confused with evidence of efficacy.

General statistical principle: observed results are estimates based on the participants and measurements included in a study, and their precision depends on the amount and quality of information. Counts from small cohorts can be informative for describing what was observed, while remaining uncertain about how frequently events would occur in a broader population. No broader rate or comparative effect should be inferred without appropriate data and analysis.

In short, the registry supports a descriptive account of reported events in the study cohorts. It does not establish treatment causation, comparative safety, or efficacy. Missing analysis details and unreported outcome results further limit the conclusions that can be drawn from the record.

13. Why This Trial Matters Statistically

Early-phase studies can provide structured observations about safety, tolerability, and pharmacokinetics while a treatment is being evaluated. This study’s sequential dose cohorts offer a record of safety events associated in time with single intradiscal doses of KTP-001. Recording events by cohort makes the observed counts visible across the planned dose levels without making them a randomized comparison.

The statistical distinction between description and inference matters. A count can faithfully describe what the registry records while leaving substantial uncertainty about the underlying event frequency. Without a control group, it is not possible to separate treatment-associated events from background events using a direct between-group comparison. Without randomization, differences between cohorts may reflect factors other than dose. These limits apply even when the numerical pattern appears orderly.

The record also illustrates why the analysis plan and outcome reporting matter. A safety endpoint spanning adverse events, imaging, examinations, and vital signs includes several kinds of observations. Readers need results, definitions, follow-up information, and analysis methods to assess the completeness and precision of the evidence. Those details are not all reported in the registry record.

The study is therefore statistically useful as a descriptive account of a sequential dose study, not as a controlled estimate of comparative safety or efficacy. Its counts can inform questions for subsequent investigation, but they do not answer those questions by themselves. A clear distinction between observed data, uncertain estimates, and causal conclusions is essential when interpreting uncontrolled early-phase evidence.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation is the absence of a control group. The study was also non-randomized and open-label. Accordingly, the cohort counts cannot provide a randomized comparison, and the registry entries do not support attributing observed events to KTP-001. Differences between dose cohorts may reflect factors other than dose.

The registry describes sequential dose cohorts but does not report detailed rules for enrollment progression, dose escalation, or safety review between cohorts. It also does not report participant eligibility criteria beyond lumbar disc herniation, baseline characteristics, or cohort-selection procedures. These omissions limit assessment of how comparable the cohorts were and how broadly the observations might apply.

The primary safety outcome covers adverse events, imaging, X-ray imaging, examinations, and vital signs, but complete results for those assessment types are not reported in the registry record for this analysis. The registry entries also do not report event attribution, severity classifications beyond the serious-event counts, follow-up completeness, missing-data handling, or analysis populations. The relationship between listed serious-event terms and particular cohorts is not reported.

No inferential analyses are reported in the registry entries. There are no reported uncertainty intervals, adjusted estimates, or efficacy results to interpret. The sample-size assumptions are described as a planning illustration rather than the study’s own design, and the original sample-size justification is not reported in the registry record. These limitations mean the available record supports a narrow descriptive reading of the safety counts, rather than comparative or causal conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate Safety and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation — NCT01978912.
• Registry record last updated 2020-02-11; status last verified 2020-02.
• Results first posted 2020-02-05.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry identifies NCT01978912 as a completed Phase 1 and Phase 2 study sponsored by Teijin America, Inc. It enrolled 24 subjects with lumbar disc herniation and evaluated KTP-001 in an open-label, non-controlled, non-randomized sequential design. Participants received one-time intradiscal doses in cohorts at 5 μg/disc, 15 μg/disc, 50 μg/disc, or 150 μg/disc.

The primary outcome assessed safety through adverse events, MRI, X-ray imaging, physical examination, neurologic examination, and vital signs over 24 months. The registry reports serious adverse-event counts of 1 of 6, 2 of 6, 1 of 6, and 0 of 6 across the cohorts, with zero deaths in each cohort. It also lists other adverse-event counts and serious adverse-event terms. Because there was no randomized control group, these data are descriptive and do not establish treatment causation or comparative effects. Efficacy results, detailed analysis methods, and several outcome and missing-data details are not reported in the registry record.