Clinical Trial Results:
A Randomized, Double-blind, Placebo-controlled Study of ALPN-101 in Systemic Lupus Erythematosus
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Summary
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EudraCT number |
2020-004047-86 |
Trial protocol |
FR PL ES HU |
Global end of trial date |
09 Jul 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Jul 2025
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First version publication date |
23 Jul 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AIS-A03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04835441 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
IND Number: 146045 | ||
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Sponsors
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Sponsor organisation name |
Alpine Immune Sciences, Inc.a Vertex Company
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Sponsor organisation address |
188 East Blaine Street, Suite 200, Seattle, WA, United States, 98102
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Public contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
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Scientific contact |
Medical Monitor, Vertex Pharmaceuticals Incorporated, +1 617-341-6777, medicalinfo@vrtx.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
08 Oct 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 Jul 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Jul 2024
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the safety and tolerability of ALPN-101 compared to placebo in subjects with moderate to severe active SLE
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Protection of trial subjects |
The study was conducted in accordance with the ethical principles stated in the Declaration of Helsinki and the International Conference on Harmonization (ICH) Guideline for Good Clinical Practice (GCP).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Jun 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Poland: 9
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Country: Number of subjects enrolled |
France: 1
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Country: Number of subjects enrolled |
Hungary: 4
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Country: Number of subjects enrolled |
United States: 58
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Country: Number of subjects enrolled |
Taiwan: 4
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Worldwide total number of subjects |
76
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EEA total number of subjects |
14
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
71
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||
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Pre-assignment
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Screening details |
The study was conducted in subjects with active systemic lupus erythematosus (SLE) aged 18 years and older. | |||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Investigator, Carer, Assessor, Subject | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ALPN-101 (Acazicolcept) | |||||||||||||||||||||
Arm description |
Subjects received a weight-based dose of 3 milligrams/kilogram (mg/kg) ALPN-101 once every 2 weeks(Q2W) up to 24 weeks. | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
Acazicolcept
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Investigational medicinal product code |
ALPN-101
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received ALPN-101 infusion over approximately 30 minutes
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Arm title
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Placebo | |||||||||||||||||||||
Arm description |
Subjects received placebo matched to ALPN-101 up to 24 weeks. | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Subjects received placebo matched to ALPN-101 up to 24 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
ALPN-101 (Acazicolcept)
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Reporting group description |
Subjects received a weight-based dose of 3 milligrams/kilogram (mg/kg) ALPN-101 once every 2 weeks(Q2W) up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received placebo matched to ALPN-101 up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
ALPN-101 (Acazicolcept)
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Reporting group description |
Subjects received a weight-based dose of 3 milligrams/kilogram (mg/kg) ALPN-101 once every 2 weeks(Q2W) up to 24 weeks. | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects received placebo matched to ALPN-101 up to 24 weeks. | ||
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End point title |
Safety and Tolerability as Assessed by Number of Subjects With Treatment- Emergent Adverse Events (TEAEs) andSerious Adverse Events (SAEs) [1] | |||||||||||||||
End point description |
Safety set included all subjects who received at least 1 dose of study drug in the treatment period.
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End point type |
Primary
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End point timeframe |
Day 1 up to Safety follow-up (up to 28 weeks)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics were planned. No statistical comparisons were planned for the primary safety endpoint. |
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Percentage of Subjects Achieving a Systemic Lupus Erythematosus (SLE) responder index (SRI)-4 | ||||||||||||
End point description |
The SRI-4 is a composite index of SLE disease improvement that consists of scores derived from the SLE Disease Activity Index 2000 (SLEDAI-2K), the British Isles Lupus Assessment Group (BILAG) 2004 Index, and the Physician’s Global Assessment (PGA). Subjects classified as responder if they met all of the following criteria: 1) ≥ 4-point reduction in the SLEDAI-2K total score; 2) no new severe disease activity or more than 1 new moderate organ score (BILAG B) compared with baseline 3) No worsening from baseline in subjects’ lupus disease activity (i.e., increase of ≥0.3 0 on a 3-point scale) in PGA. Modified intent-to-treat population (mITT), includes all randomized subjects who received any amount of study drug and have completed at least one post-baseline disease assessment. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
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End point type |
Primary
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End point timeframe |
At Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
ALPN-101 (Acazicolcept) v Placebo
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.107 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
Percentage of Subjects Achieving a British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response | ||||||||||||
End point description |
The BICLA is a responder index developed to measure response to therapy, and it includes scores from the BILAG,SLEDAI-2K, and Physician’s Global Assessment (PGA). BICLA response is defined as: 1) at least 1 gradation of improvement in baseline BILAG 2004 scores in all body systems with moderate disease activity at entry (e.g, all B [mild disease] scores falling to C [Stable and mild], or D [no activity]); 2) no new BILAG A or more than 1 new BILAG B scores; 3) no worsening of total SLEDAI-2K score from baseline; 4) ≤ 10% deterioration in PGA score. The PGA is measured on a 0 to 100 mm scale with score 0 to be No Disease Activity and score 100 to be the most Severe Disease Activity. mITT. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint
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End point type |
Primary
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End point timeframe |
At Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
ALPN-101 (Acazicolcept) v Placebo
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.308 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
Annualized flare rate by British Isles Lupus Assessment Group (BILAG)-2004 flare index | ||||||||||||
End point description |
The BILAG-2004 index covers 86 item assessment across 9 organ systems. Each question is answered as 0-not present, 1-improving, 2-same, 3-worse, to 4-new. The BILAG-2004 index categorizes disease activity in each organ system into five different levels from A to E. Grade A : disease-modifying treatment, Grade B: mild, reversible problems requiring symptomatic therapy, Grade C: mild stable disease, and grade D: no disease activity, but suggests the organ system had previously been affected. Grade E: no current or previous disease activity. Higher scores indicate more severe disease activity. Annualized flare rated is defined as the number of flares observed during the treatment period divided by the flare exposure time in days multiplied by 365.25. mITT. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
Placebo v ALPN-101 (Acazicolcept)
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.442 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Time-to-first Flare by BILAG-2004 Flare Index | ||||||||||||
End point description |
Time-to-first SLE flare is defined as the number of days from the administration of first dose to the first occurrence of flare. A flare was defined as having an adjudicated BILAG A or B score in any of the 8 organ systems during treatment. The BILAG disease activity index evaluates SLE activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone greater than 20 mg daily or immunosuppressants); BILAG B: Disease less active than in "A", mild reversible problems requiring only symptomatic therapy such as antimalarials, NSAIDs, or prednisone less than 20mg day; BILAG C: Stable mild disease; BILAG D: System previously affected but now inactive; BILAG E: System never involved. mITT. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
ALPN-101 (Acazicolcept) v Placebo
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.788 | ||||||||||||
Method |
Kaplan-Meier methods | ||||||||||||
Confidence interval |
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End point title |
Percentage of Subjects Achieving Lupus Low Disease Activity State (LLDAS) | ||||||||||||
End point description |
The LLDAS is a composite measure designed to identify patients achieving a state of low disease activity. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (CNS, vascular, renal, cardiorespiratory and constitutional); where "no activity" is defined as all items of SLEDAI-2K within these major organ systems equal to 0. (2) no new features of lupus disease activity compared to previous occurred visit, where the "new feature" is defined as any of the SLEDAI-2K 24 items changed from 0 to greater than 0; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily; and allowance for maintenance doses of immunosuppressive drugs and approved biological agents. mITT. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
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End point type |
Secondary
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End point timeframe |
At Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
ALPN-101 (Acazicolcept) v Placebo
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.792 | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Confidence interval |
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End point title |
Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Total Score | ||||||||||||
End point description |
SLEDAI-2K score is used to identify patients with more active disease at study enrollment. Total score is the sum of weighted scores for each organ system. For each system organ with baseline score >0, improvement in SLEDAI-2K improvement is achieved by meeting all the following criteria: • Reduction in system organ scores among subjects with baseline SLEDAI-2K scores >0 •No early discontinuation of study drug • No use of restricted medications beyond the protocol-allowed threshold before assessment SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Baseline was defined as core study screening visit. mITT. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
Placebo v ALPN-101 (Acazicolcept)
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.302 | ||||||||||||
Method |
Mixed models for repeated measures | ||||||||||||
Confidence interval |
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End point title |
Cumulative prednisone-equivalent dose use through Day 169 | ||||||||||||
End point description |
mITT. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline Through Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
ALPN-101 (Acazicolcept) v Placebo
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Number of subjects included in analysis |
74
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.506 | ||||||||||||
Method |
ANOVA | ||||||||||||
Confidence interval |
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End point title |
Percentage of Subjects Achievement of ≥ 50% Reduction In CLASI Activity Score In Subjects With Baseline CLASIActivity Score ≥ 8 | ||||||||||||
End point description |
CLASI Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and nonscarring alopecia. Evaluation of erythema and scale/hyperkeratosis is based on a table: rows represent anatomical areas and columns represent major clinical symptoms. The extent of involvement for each of the skin symptoms is documented for each anatomic area. The total score ranges from 0-70, with higher scores indicating more severe skin disease. 50% reduction in CLASI activity score compared to baseline was defined by meeting all of the following criteria: • Achieve ≥50% reduction of CLASI activity score at Day 169 compared to baseline. mITT. Here "Number of subjects analysed" signifies those subjects who were evaluated for this specific endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to Day 169
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
ALPN-101 (Acazicolcept) v Placebo
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Number of subjects included in analysis |
21
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.659 | ||||||||||||
Method |
Fisher exact | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 up to Safety follow-up (up to 28 weeks)
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Adverse event reporting additional description |
Safety set included all subjects who received at least 1 dose of study drug in the treatment period.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
ALPN-101 (Acazicolcept)
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Reporting group description |
Subjects received a weight-based dose of 3 mg/kg ALPN-101 Q2W up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received placebo matched to ALPN-101 up to 24 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Apr 2021 |
Amended to increase the number of study drug doses from 6 to 12, with an associated extension in the treatment duration from 85 days (12 weeks) to 169 days (24 weeks) and in the overall study duration for each subject from 22 to 36 weeks. |
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29 Sep 2021 |
Amended the eligibility criteria (inclusion and exclusion) of subjects. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
