Inflammatory Bowel Disease, Iron Deficiency Anaemia, Ulcerative Colitis
Conditions
Keywords
iron deficiency, anaemia, inflammatory bowel disease, ulcerative colitis
Brief summary
The purpose of this study is to determine whether ST10-021, an oral ferric iron preparation, is safe and effective in the treatment of iron deficiency anaemia (IDA) in subjects with non-active ulcerative colitis (UC).
Detailed description
As no curative treatment is currently available for ulcerative colitis (UC), treatment options are restricted to controlling symptoms, maintaining remission and preventing relapse. As such, treatment of iron deficiency anaemia (IDA), a key symptom of the disease, is integral to the medical management of UC. Iron deficiency anaemia in UC is a chronically debilitating disorder which has a significant impact on the quality of life of affected subjects. Characteristic symptoms of IDA include chronic fatigue, headache, and subtle impairment of cognitive function. Up to one third of subjects with UC suffer from recurrent anaemia, with hospitalization required in severe cases. First line standard therapy for mild to moderate IDA in UC is typically oral ferrous products (OFP), however this is often not successful. Many subjects are intolerant and suffer from continuously occurring side effects, occasional exacerbation of inflammatory lesions and failure to correct iron deficiency. Common adverse effects of OFP include nausea, epigastric discomfort and constipation, all of which are dose-related and appear especially evident in subjects with UC. As compared to oral ferrous iron, oral ferric iron can be administered with improved tolerability and the total dose exposure of unabsorbed iron within the gastrointestinal tract is significantly reduced. In addition, the iron is retained in its chelated form if not absorbed and this may reduce the risk of irritation within the gastrointestinal tract. Clinical studies conducted to date provide preliminary evidence for the therapeutic potential of ST10-021 in patients with IDA in Inflammatory Bowel Disease, including UC. The purpose of this study is to determine whether ST10-021 is safe and effective in the treatment of IDA in subjects with non-active UC. In an effort to target an underserved population, the study will include only those subjects who have failed OFP in the past, or where OFP cannot be used.
Interventions
DRUGST10-021
30 mg capsules to be taken orally twice a day for 12 weeks
DRUGPlacebo Comparator
Matching sugar pill to be taken orally twice a day for 12 weeks
Sponsors
Shield Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Competency to understand and sign the IEC/IRB approved informed consent form prior to any study mandated procedure, and willing/able to comply with study requirements * Age ≥ 18 years * Current diagnosis of quiescent UC as defined by SCCAI score of \< 4 * Current diagnosis of IDA as defined by Hb ≥ 9.5 g/dl and \<12.0 g/dl for women and ≥ 9.5 g/dl and \<13.0 g/dl for men; ferritin \< 30 µg/l * Prior OFP failure as defined per protocol * If receiving protocol-allowed immunosuppressant must be on stable dose * Females of childbearing potential must agree to use a reliable method of contraception
Exclusion criteria
* Anaemia due to any cause other than iron deficiency * Intramuscular or intravenous injection or administration of depot iron preparation, blood infusions, or erythropoietin within 3 months * Oral iron supplementation use within 1 month * Use of immunosuppressant with known effect of anaemia induction within 1 month * Vitamin B12 or Folic Acid injection/infusion within 4 weeks * Untreated Vitamin B-12 or Folic Acid deficiency * Known hypersensitivity or allergy to ST10-021 or components of the study medication, or contraindication for treatment with iron preparations * Other chronic or acute inflammatory or infectious diseases * Creatinine \> 2.0 mg/dl * AST or ALT levels ≥ 5 times the upper limit of normal * Cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject * History of malignancy within the past 5 years (except in situ removal of basal cell carcinoma) * Significant neurologic or psychiatric symptoms resulting in disorientation, memory impairment, or inability to report accurately that might interfere with treatment compliance, study conduct or interpretation of the results * Participation in another interventional clinical study within 30 days or during the study * Inmates of a psychiatric ward, prison, or other state institution * Investigator or any other team member involved directly or indirectly in the conduct of the clinical study * Scheduled or expected hospitalization and/or surgery during the course of the study * Females who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS) | Baseline to Week 12 - double-blind phase | Primary efficacy endpoint, defined as the change in Hb concentration from Baseline to Week 12. Baseline was defined as the pre-dose Hb concentration measured at the Randomisation Visit (Week 0). Missing Randomisation Hb values were replaced by Screening Hb values, if the randomisation was within the protocol-specified window. Hb concentration (g/dL) was analysed by a central laboratory from blood samples collected at every clinic visit: Screening, Randomisation (Week 0), Weeks 4, 8, 12, 14, 16, 20, 24, 36, 48, 64, Weeks 14 to 64 were open-label. The baseline, absolute concentration and change from baseline in Hb at all post-randomisation visits were listed and summarised by week using descriptive statistics. An analysis of covariance (ANCOVA) was used to analyse the primary endpoint; this included treatment, gender and disease as factors and baseline Hb as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS) | Baseline to Week 4 - double-blind phase | ANCOVA analysis of the change in Hb concentration from Baseline to Week 4 of the double-blind phase - Full Analysis Set, multiple imputation |
| Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS) | Baseline to Week 16 - open-label phase | Change in Haemoglobin Concentration from Baseline to Week 16 (FAS), after 12-week double-blind phase and first 4 weeks of open-label ST10 treatment. |
| Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS) | Baseline to Week 20 - open-label phase | Change in Haemoglobin Concentration from Baseline to Week 20 (FAS), after 12-week double-blind phase and then 8 weeks of open-label ST10 treatment |
| Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS) | Baseline to Week 24 - open-label phase | Change in Haemoglobin Concentration from Baseline to Week 24 (FAS), after 12-week double-blind phase and then 12 weeks of open-label ST10 treatment |
| Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS) | Baseline to Week 36 - open-label phase | Change in Haemoglobin Concentration from Baseline to Week 36 (FAS), after 12-week double-blind phase and then 24 weeks of open-label ST10 treatment |
| Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS) | Baseline to Week 48 - open-label phase | Change in Haemoglobin Concentration from Baseline to Week 48 (FAS), after 12-week double-blind phase and then 36 weeks of open-label ST10 treatment |
| Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS) | Baseline to Week 64 - open-label phase | Change in Haemoglobin Concentration from Baseline to Week 64 (FAS), after 12-week double-blind phase and then 52 weeks of open-label ST10 treatment |
| Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS) | Baseline to Week 64 EOS - open-label phase | Change in Haemoglobin Concentration from Baseline to Week 64 EOS (FAS) - Week 64 was re-categorised as Week 64 EOS for those subjects who withdrew from the study early and the 'Week 64' visit was outside the visit window of 64 weeks ± 2 days |
| Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS) | Baseline to Week 16 - open-label phase | Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 16 (Full Analysis Set), after 12-week double-blind phase and first 4 weeks of open-label ST10 treatment |
| Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS) | Baseline to Week 36 - open-label phase | Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 36 (Full Analysis Set), after 12-week double-blind phase and 24 weeks of open-label ST10 treatment |
| Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS) | Baseline to Week 64 - open-label phase | Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 64 (Full Analysis Set), after 12-week double-blind phase and 52 weeks of open-label ST10 treatment |
| Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS) | Baseline to Week 12 - double-blind phase | Logistic regression analysis of proportion of subjects that achieved Hb concentration within normal range at Week 12 - end of double-blind phase |
| Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 - double-blind phase | Logistic regression analysis of proportion of subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 in the double-blind phase |
| Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Baseline to Week 12 - double-blind phase | Logistic regression analysis of proportion of subjects that achieved ≥2 g/dL change from baseline in Hb concentration at Week 12 in the double-blind phase |
| Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS) | Baseline to Week 8 - double-blind phase | ANCOVA analysis of Change in Hb concentration from Baseline to Week 8 of double-blind phase - FAS, multiple imputation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF) | Baseline to Week 12 - double-blind phase | ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the FAS LOCF - Change in Haemoglobin Concentration from Baseline to Week 12 |
| Change in Serum Ferritin Concentration From Baseline to Week 12 (Full Analysis Set, FAS) | Baseline to Week 12 - double-blind phase | Change in serum Ferritin concentration from Baseline to Week 12 (Full Analysis Set), after 12-week double-blind phase |
| Change in Serum Ferritin Concentration From Baseline to Week 64 (Full Analysis Set, FAS) | Baseline to Week 64 - open-label phase | Change in serum Ferritin concentration from Baseline to Week 64 (FAS), after 12-week double-blind phase and 52 weeks open-label ST10 treatment |
| Change in Serum TSAT% From Baseline to Week 12 (Full Analysis Set, FAS) | Baseline to Week 12 - double-blind phase | Change in serum TSAT% from Baseline to Week 12 (FAS), after 12-week double-blind phase |
| Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 12 (Full Analysis Set, FAS) | Week 12 - double-blind phase | Irritable Bowel Disease Questionnaire (IBDQ) score at Week 12 (FAS), end of double-blind phase. The IBDQ was developed as an activity index for determining the effect of Ulcerative Colitis symptoms on perceived quality of life. It is a 32-item questionnaire with four dimensions: bowel function, emotional status, systemic symptoms and social function. Total IBDQ score ranges from 32 to 224, with higher scores indicating better quality of life. The score of patients in remission usually is between 170 and 190. |
| Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 64 (Full Analysis Set, FAS) | Week 64 - open-label phase | Irritable Bowel Disease Questionnaire (IBDQ) score at Week 64 (FAS), after 12-week double-blind phase and 52 weeks of open-label ST10 treatment. The IBDQ was developed as an activity index for determining the effect of Ulcerative Colitis symptoms on perceived quality of life. It is a 32-item questionnaire with four dimensions: bowel function, emotional status, systemic symptoms and social function. Total IBDQ score ranges from 32 to 224, with higher scores indicating better quality of life. The score of patients in remission usually is between 170 and 190. |
| Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 12 (Full Analysis Set, FAS) | Baseline to Week 12 - double-blind phase | Change from baseline in Simple Clinical Colitis Activity Index (SCCAI) score at Week 12 (FAS), end of double-blind phase (in subjects with UC). The SCCAI is a diagnostic and research questionnaire used to assess the severity of symptoms in people who suffer from UC. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher. The score is determined by asking the person with UC questions regarding: * bowel frequency at day/night * urgency of defecation * blood in stool * general health * extracolonic manifestations |
| Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 64 (Full Analysis Set) | Baseline to Week 64 - open-label phase | Change from baseline in Simple Clinical Colitis Activity Index (SCCAI) score at Week 64 (FAS), after 12-week double-blind phase and 52 weeks open-label ST10 treatment (in participants with UC only). The SCCAI is a diagnostic and research questionnaire used to assess the severity of symptoms in people who suffer from UC. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher. The score is determined by asking the person with UC questions regarding: * bowel frequency at day/night * urgency of defecation * blood in stool * general health * extracolonic manifestations |
| Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS) | Baseline to Week 12 - double-blind phase | ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the PPAS - Change in Haemoglobin Concentration from Baseline to Week 12 |
| Change in Serum TSAT% From Baseline to Week 64 (Full Analysis Set, FAS) | Baseline to Week 64 - open-label phase | Change in serum TSAT% from Baseline to Week 64 (Full Analysis Set), after 12-week double-blind phase and 52 weeks open-label ST10 treatment |
Participant flow
Recruitment details
Potential subjects were selected from the general population attending each centre in UK, DE, AT or HU for routine care of their IBD and anaemia. Individuals interested in participating were invited for the Screening visit in order to assess eligibility. Written informed consent was obtained prior to conducting any study specific assessments.
Pre-assignment details
Subjects were males or females aged ≥18 years with a confirmed diagnosis of UC, required to be in remission have a mild-to-moderate UC (defined by SCCAI score \<4 at entry); mild-to-moderate IDA (Hb concentration ≥9.5 g/dL and \<12.0 g/dL for females and ≥9.5 g/dL and \<13.0 g/dL for males; serum ferritin levels \<30 μg/L at Screening.
Participants by arm
| Arm | Count |
|---|---|
| ST10 ST10: 30 mg Ferric Maltol capsules taken orally twice a day during a 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase. | 64 |
| Placebo Matching Placebo capsules taken orally twice a day during a 12-week double-blind phase. For study participants in the UK, DE and HU only, the 12-week double-blind phase was followed by a 52-week open-label ST10 extension treatment phase. | 64 |
| Total | 128 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Double-blind Phase | Adverse Event | 6 | 4 | 0 | 0 |
| Double-blind Phase | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Double-blind Phase | Protocol Violation | 0 | 1 | 0 | 0 |
| Double-blind Phase | Withdrawal by Subject | 3 | 5 | 0 | 0 |
| Open-label Phase | Adverse Event | 0 | 0 | 8 | 4 |
| Open-label Phase | Physician Decision | 0 | 0 | 2 | 1 |
| Open-label Phase | Pregnancy | 0 | 0 | 1 | 0 |
| Open-label Phase | Withdrawal by Subject | 0 | 0 | 1 | 6 |
| Open-label Phase | Worsening of IBD | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | ST10 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 63 Participants | 62 Participants | 125 Participants |
| Age, Continuous | 38.5 years STANDARD_DEVIATION 12.3 | 40.1 years STANDARD_DEVIATION 13.52 | 39.2 years STANDARD_DEVIATION 12.9 |
| Duration of ulcerative colitis (years) | 10.99 years STANDARD_DEVIATION 11.43 | 9.0 years STANDARD_DEVIATION 8.28 | 9.99 years STANDARD_DEVIATION 9.8 |
| Haemoglobin concentration at baseline | 11.1 g/dL STANDARD_DEVIATION 0.85 | 11 g/dL STANDARD_DEVIATION 1.03 | 11.05 g/dL STANDARD_DEVIATION 0.93 |
| Irritable Bowel Disease Questionnaire (IBDQ) score at baseline | 171.0 score on a scale STANDARD_DEVIATION 33.56 | 175.0 score on a scale STANDARD_DEVIATION 30.92 | 173.02 score on a scale STANDARD_DEVIATION 32.23 |
| Region of Enrollment Austria | 6 participants | 4 participants | 10 participants |
| Region of Enrollment Germany | 32 participants | 35 participants | 67 participants |
| Region of Enrollment Hungary | 15 participants | 11 participants | 26 participants |
| Region of Enrollment United Kingdom | 10 participants | 15 participants | 25 participants |
| Serum Ferritin concentration at baseline | 8.2 μg/L STANDARD_DEVIATION 6.5 | 8.6 μg/L STANDARD_DEVIATION 6.8 | 8.4 μg/L STANDARD_DEVIATION 6.6 |
| Sex: Female, Male Female | 43 Participants | 40 Participants | 83 Participants |
| Sex: Female, Male Male | 21 Participants | 24 Participants | 45 Participants |
| Simple Clinical Colitis Activity Index (SCCAI) score at baseline | 1.4 score on a scale | 1.8 score on a scale | 1.6 score on a scale |
| Time since last IBD flare-up (months) | 21.51 months STANDARD_DEVIATION 38.46 | 24.8 months STANDARD_DEVIATION 59.16 | 23.2 months STANDARD_DEVIATION 48.4 |
| Time since last OFP dose (months) | 33.34 months STANDARD_DEVIATION 44.04 | 36.17 months STANDARD_DEVIATION 40.1 | 34.76 months STANDARD_DEVIATION 41.7 |
| TSAT% at baseline | 9.5 percentage STANDARD_DEVIATION 7.5 | 10.6 percentage STANDARD_DEVIATION 11.7 | 10.05 percentage STANDARD_DEVIATION 9.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 64 | 0 / 50 | 0 / 47 |
| other Total, other adverse events | 39 / 64 | 46 / 64 | 40 / 50 | 35 / 47 |
| serious Total, serious adverse events | 1 / 64 | 2 / 64 | 8 / 50 | 2 / 47 |
Outcome results
Primary
Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS)
Primary efficacy endpoint, defined as the change in Hb concentration from Baseline to Week 12. Baseline was defined as the pre-dose Hb concentration measured at the Randomisation Visit (Week 0). Missing Randomisation Hb values were replaced by Screening Hb values, if the randomisation was within the protocol-specified window. Hb concentration (g/dL) was analysed by a central laboratory from blood samples collected at every clinic visit: Screening, Randomisation (Week 0), Weeks 4, 8, 12, 14, 16, 20, 24, 36, 48, 64, Weeks 14 to 64 were open-label. The baseline, absolute concentration and change from baseline in Hb at all post-randomisation visits were listed and summarised by week using descriptive statistics. An analysis of covariance (ANCOVA) was used to analyse the primary endpoint; this included treatment, gender and disease as factors and baseline Hb as a covariate.
Time frame: Baseline to Week 12 - double-blind phase
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS) | 2.26 g/dL | Standard Deviation 1.184 |
| Placebo | Change in Haemoglobin (Hb) Concentration From Baseline to Week 12 (Full Analysis Set, FAS) | 0.01 g/dL | Standard Deviation 0.764 |
Comparison: ANCOVA for primary endpoint, Change in Hb concentration from Baseline to Week 12 in double-blind phase, FASp-value: <0.0001ANCOVA
Secondary
Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS)
Change in Haemoglobin Concentration from Baseline to Week 16 (FAS), after 12-week double-blind phase and first 4 weeks of open-label ST10 treatment.
Time frame: Baseline to Week 16 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS) | 2.34 g/dL | Standard Deviation 1.281 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 16 (Full Analysis Set, FAS) | 1.04 g/dL | Standard Deviation 1.023 |
Secondary
Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS)
Change in Haemoglobin Concentration from Baseline to Week 20 (FAS), after 12-week double-blind phase and then 8 weeks of open-label ST10 treatment
Time frame: Baseline to Week 20 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS) | 2.45 g/dL | Standard Deviation 1.213 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 20 (Full Analysis Set, FAS) | 1.46 g/dL | Standard Deviation 1.056 |
Secondary
Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS)
Change in Haemoglobin Concentration from Baseline to Week 24 (FAS), after 12-week double-blind phase and then 12 weeks of open-label ST10 treatment
Time frame: Baseline to Week 24 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS) | 2.68 g/dL | Standard Deviation 1.127 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 24 (Full Analysis Set, FAS) | 1.87 g/dL | Standard Deviation 1.195 |
Secondary
Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS)
Change in Haemoglobin Concentration from Baseline to Week 36 (FAS), after 12-week double-blind phase and then 24 weeks of open-label ST10 treatment
Time frame: Baseline to Week 36 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS) | 2.85 g/dL | Standard Deviation 1.227 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 36 (Full Analysis Set, FAS) | 2.17 g/dL | Standard Deviation 1.048 |
Secondary
Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS)
Change in Haemoglobin Concentration from Baseline to Week 48 (FAS), after 12-week double-blind phase and then 36 weeks of open-label ST10 treatment
Time frame: Baseline to Week 48 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS) | 3.09 g/dL | Standard Deviation 1.339 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 48 (Full Analysis Set, FAS) | 2.0 g/dL | Standard Deviation 1.191 |
Secondary
Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS)
Change in Haemoglobin Concentration from Baseline to Week 64 EOS (FAS) - Week 64 was re-categorised as Week 64 EOS for those subjects who withdrew from the study early and the 'Week 64' visit was outside the visit window of 64 weeks ± 2 days
Time frame: Baseline to Week 64 EOS - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS) | 1.32 g/dL | Standard Deviation 1.713 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 64 EOS (Full Analysis Set, FAS) | 0.52 g/dL | Standard Deviation 1.417 |
Secondary
Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)
Change in Haemoglobin Concentration from Baseline to Week 64 (FAS), after 12-week double-blind phase and then 52 weeks of open-label ST10 treatment
Time frame: Baseline to Week 64 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS) | 3.07 g/dL | Standard Deviation 1.457 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 64 (Full Analysis Set, FAS) | 2.19 g/dL | Standard Deviation 1.605 |
Secondary
Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS)
ANCOVA analysis of the change in Hb concentration from Baseline to Week 4 of the double-blind phase - Full Analysis Set, multiple imputation
Time frame: Baseline to Week 4 - double-blind phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS) | 1.08 g/dL | Standard Deviation 0.676 |
| Placebo | Change in Hb Concentration From Baseline to Week 4 (Full Analysis Set, FAS) | 0 g/dL | Standard Deviation 0.67 |
Comparison: ANCOVA analysis of the change in Hb concentration from Baseline to Week 4 of the double-blind phase - Full Analysis Set, multiple imputationp-value: <0.0001ANCOVA
Secondary
Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS)
ANCOVA analysis of Change in Hb concentration from Baseline to Week 8 of double-blind phase - FAS, multiple imputation
Time frame: Baseline to Week 8 - double-blind phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS) | 1.79 g/dL | Standard Deviation 1.037 |
| Placebo | Change in Hb Concentration From Baseline to Week 8 (Full Analysis Set, FAS) | 0.04 g/dL | Standard Deviation 0.722 |
Comparison: ANCOVA analysis of Change in Hb concentration from Baseline to Week 8 of double-blind phase - FAS, multiple imputationp-value: <0.0001ANCOVA
Secondary
Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)
Logistic regression analysis of proportion of subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 in the double-blind phase
Time frame: Subjects that achieved ≥1 g/dL change from baseline in Hb concentration at Week 12 - double-blind phase
Population: Full Analysis Set (FAS)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ST10 | Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Yes | 50 Participants |
| ST10 | Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | No | 14 Participants |
| Placebo | Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Yes | 7 Participants |
| Placebo | Proportion of Subjects That Achieved ≥1 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | No | 57 Participants |
Secondary
Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS)
Logistic regression analysis of proportion of subjects that achieved ≥2 g/dL change from baseline in Hb concentration at Week 12 in the double-blind phase
Time frame: Baseline to Week 12 - double-blind phase
Population: FAS
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ST10 | Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Yes | 36 Participants |
| ST10 | Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | No | 28 Participants |
| Placebo | Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | Yes | 0 Participants |
| Placebo | Proportion of Subjects That Achieved ≥2 g/dL Change From Baseline in Hb Concentration at Week 12 (Full Analysis Set, FAS) | No | 64 Participants |
Secondary
Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS)
Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 16 (Full Analysis Set), after 12-week double-blind phase and first 4 weeks of open-label ST10 treatment
Time frame: Baseline to Week 16 - open-label phase
Population: FAS
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ST10 | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS) | Yes | 36 Participants |
| ST10 | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS) | No | 10 Participants |
| Placebo | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS) | Yes | 17 Participants |
| Placebo | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 16 (Full Analysis Set, FAS) | No | 28 Participants |
Secondary
Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS)
Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 36 (Full Analysis Set), after 12-week double-blind phase and 24 weeks of open-label ST10 treatment
Time frame: Baseline to Week 36 - open-label phase
Population: FAS
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ST10 | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS) | Yes | 35 Participants |
| ST10 | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS) | No | 6 Participants |
| Placebo | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS) | Yes | 29 Participants |
| Placebo | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 36 (Full Analysis Set, FAS) | No | 7 Participants |
Secondary
Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS)
Proportion of subjects that achieved Haemoglobin Concentration within normal range at Week 64 (Full Analysis Set), after 12-week double-blind phase and 52 weeks of open-label ST10 treatment
Time frame: Baseline to Week 64 - open-label phase
Population: FAS
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ST10 | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS) | Yes | 31 Participants |
| ST10 | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS) | No | 5 Participants |
| Placebo | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS) | Yes | 30 Participants |
| Placebo | Proportion of Subjects That Achieved Haemoglobin Concentration Within Normal Range at Week 64 (Full Analysis Set, FAS) | No | 6 Participants |
Secondary
Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS)
Logistic regression analysis of proportion of subjects that achieved Hb concentration within normal range at Week 12 - end of double-blind phase
Time frame: Baseline to Week 12 - double-blind phase
Population: FAS
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ST10 | Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS) | Yes | 42 Participants |
| ST10 | Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS) | No | 22 Participants |
| Placebo | Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS) | Yes | 8 Participants |
| Placebo | Proportion of Subjects That Achieved Hb Concentration Within Normal Range at Week 12 (Full Analysis Set, FAS) | No | 56 Participants |
Other Pre-specified
Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 12 (Full Analysis Set, FAS)
Change from baseline in Simple Clinical Colitis Activity Index (SCCAI) score at Week 12 (FAS), end of double-blind phase (in subjects with UC). The SCCAI is a diagnostic and research questionnaire used to assess the severity of symptoms in people who suffer from UC. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher. The score is determined by asking the person with UC questions regarding: * bowel frequency at day/night * urgency of defecation * blood in stool * general health * extracolonic manifestations
Time frame: Baseline to Week 12 - double-blind phase
Population: FAS - participants with UC only
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ST10 | Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 12 (Full Analysis Set, FAS) | 0 score on a scale |
| Placebo | Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 12 (Full Analysis Set, FAS) | 0 score on a scale |
Other Pre-specified
Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 64 (Full Analysis Set)
Change from baseline in Simple Clinical Colitis Activity Index (SCCAI) score at Week 64 (FAS), after 12-week double-blind phase and 52 weeks open-label ST10 treatment (in participants with UC only). The SCCAI is a diagnostic and research questionnaire used to assess the severity of symptoms in people who suffer from UC. The calculated score ranges from 0 to 19, where active disease is a score of 5 or higher. The score is determined by asking the person with UC questions regarding: * bowel frequency at day/night * urgency of defecation * blood in stool * general health * extracolonic manifestations
Time frame: Baseline to Week 64 - open-label phase
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ST10 | Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 64 (Full Analysis Set) | 0 score on a scale |
| Placebo | Change From Baseline in Simple Clinical Colitis Activity Index (SCCAI) Score at Week 64 (Full Analysis Set) | 0 score on a scale |
Other Pre-specified
Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF)
ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the FAS LOCF - Change in Haemoglobin Concentration from Baseline to Week 12
Time frame: Baseline to Week 12 - double-blind phase
Population: FAS LOCF - sensitivity analysis of primary endpoint
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF) | 2.11 g/dL | Standard Error 0.12 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 12 (Full Analysis Set [FAS] LOCF) | -0.03 g/dL | Standard Error 0.12 |
Comparison: ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the FAS LOCF - Change in Haemoglobin Concentration from Baseline to Week 12p-value: <0.0001ANCOVA
Other Pre-specified
Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS)
ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the PPAS - Change in Haemoglobin Concentration from Baseline to Week 12
Time frame: Baseline to Week 12 - double-blind phase
Population: Per-Protocol Analysis Set - sensitivity analysis of primary endpoint
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS) | 2.23 g/dL | Standard Error 0.13 |
| Placebo | Change in Haemoglobin Concentration From Baseline to Week 12 (Per Protocol Analysis Set, PPAS) | 0.05 g/dL | Standard Error 0.13 |
Comparison: ANCOVA sensitivity analysis of the Primary efficacy endpoint analysis on the PPASp-value: <0.0001ANCOVA
Other Pre-specified
Change in Serum Ferritin Concentration From Baseline to Week 12 (Full Analysis Set, FAS)
Change in serum Ferritin concentration from Baseline to Week 12 (Full Analysis Set), after 12-week double-blind phase
Time frame: Baseline to Week 12 - double-blind phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Serum Ferritin Concentration From Baseline to Week 12 (Full Analysis Set, FAS) | 17.3 μg/dL | Standard Deviation 28.3 |
| Placebo | Change in Serum Ferritin Concentration From Baseline to Week 12 (Full Analysis Set, FAS) | 1.2 μg/dL | Standard Deviation 7.85 |
Other Pre-specified
Change in Serum Ferritin Concentration From Baseline to Week 64 (Full Analysis Set, FAS)
Change in serum Ferritin concentration from Baseline to Week 64 (FAS), after 12-week double-blind phase and 52 weeks open-label ST10 treatment
Time frame: Baseline to Week 64 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Serum Ferritin Concentration From Baseline to Week 64 (Full Analysis Set, FAS) | 60.4 μg/dL | Standard Deviation 93.35 |
| Placebo | Change in Serum Ferritin Concentration From Baseline to Week 64 (Full Analysis Set, FAS) | 36.6 μg/dL | Standard Deviation 46.8 |
Other Pre-specified
Change in Serum TSAT% From Baseline to Week 12 (Full Analysis Set, FAS)
Change in serum TSAT% from Baseline to Week 12 (FAS), after 12-week double-blind phase
Time frame: Baseline to Week 12 - double-blind phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Serum TSAT% From Baseline to Week 12 (Full Analysis Set, FAS) | 18.0 % serum TSAT | Standard Deviation 20.17 |
| Placebo | Change in Serum TSAT% From Baseline to Week 12 (Full Analysis Set, FAS) | -0.4 % serum TSAT | Standard Deviation 7.82 |
Other Pre-specified
Change in Serum TSAT% From Baseline to Week 64 (Full Analysis Set, FAS)
Change in serum TSAT% from Baseline to Week 64 (Full Analysis Set), after 12-week double-blind phase and 52 weeks open-label ST10 treatment
Time frame: Baseline to Week 64 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Change in Serum TSAT% From Baseline to Week 64 (Full Analysis Set, FAS) | 18.8 % serum TSAT | Standard Deviation 12.46 |
| Placebo | Change in Serum TSAT% From Baseline to Week 64 (Full Analysis Set, FAS) | 17.7 % serum TSAT | Standard Deviation 16.2 |
Other Pre-specified
Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 12 (Full Analysis Set, FAS)
Irritable Bowel Disease Questionnaire (IBDQ) score at Week 12 (FAS), end of double-blind phase. The IBDQ was developed as an activity index for determining the effect of Ulcerative Colitis symptoms on perceived quality of life. It is a 32-item questionnaire with four dimensions: bowel function, emotional status, systemic symptoms and social function. Total IBDQ score ranges from 32 to 224, with higher scores indicating better quality of life. The score of patients in remission usually is between 170 and 190.
Time frame: Week 12 - double-blind phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 12 (Full Analysis Set, FAS) | 178.3 score on a scale | Standard Deviation 32.36 |
| Placebo | Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 12 (Full Analysis Set, FAS) | 176.3 score on a scale | Standard Deviation 31.5 |
Other Pre-specified
Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 64 (Full Analysis Set, FAS)
Irritable Bowel Disease Questionnaire (IBDQ) score at Week 64 (FAS), after 12-week double-blind phase and 52 weeks of open-label ST10 treatment. The IBDQ was developed as an activity index for determining the effect of Ulcerative Colitis symptoms on perceived quality of life. It is a 32-item questionnaire with four dimensions: bowel function, emotional status, systemic symptoms and social function. Total IBDQ score ranges from 32 to 224, with higher scores indicating better quality of life. The score of patients in remission usually is between 170 and 190.
Time frame: Week 64 - open-label phase
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ST10 | Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 64 (Full Analysis Set, FAS) | 180.7 score on a scale | Standard Deviation 30.14 |
| Placebo | Irritable Bowel Disease Questionnaire (IBDQ) Score at Week 64 (Full Analysis Set, FAS) | 177.2 score on a scale | Standard Deviation 36.97 |